The objectives of this project concern analysis of the consequences of manipulation of the hormonal and humoral milieu on brain development in the rat, based on the hypothesis that certain hormones (glucocorticoids, thyroid hormone) and neurotransmitters acting like hormones (the monoamines) may modulate various aspects of neurogenesis during the pre- and postnatal period. The first part of this investigation concerns a comparison of the effects of postnatal administration of glucocorticoids and thyroxine (both of which produce cell deficits) on cell proliferation and neuronal differentiation in the cerebellar cortex and hippocampus, using H3-thymidine autoradiography, histochemical, light and electron microscopic methods. The second part of this program is designed to test the hypothesis that early forming/monoamine neurons may influence the onset of differentiation of their ultimate target cells in the neural tube using H3-thymidine autoradiography. Pilot studies have already indicated that treatment of the pregnant mother with monoamine depleting drugs can change the time of differentiation of monoamine target cells. These studies will be extended and compared to the effects of monoamine precursors using the same methods. Since these pilot studies also indicated that maternal stress may influence the differentiation of monoamine target cells by increasing monoamine synthesis in the embryo, perhaps via the mediation of elevated levels of maternal glucocorticoids, the effects of administration of this hormone to the pregnant female on fetal brain development will also be explored. Such studies may provide model systems within which to accurately test the effects of drugs, hormones and environmental influences on pre-and post-natal neurogenesis.